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How is bacitracin administered?
Nephrotoxic if given systemically, so given parenterally
Most commonly topically; used intramuscularly in infants with staphylococcal infections (RARE)
Poor absorption following topical application. Marketed as ointment with polymixin B (Polysporin) or neomycin (Neosporin); often used for dermatological and ophthalmic infection
How does vancomycin work? How is it classified?
Inhibits bacterial wall synthesis by inhibiting synthesis of wall phospholipids; also inhibits peptidoglycan cross-linking
It is bactericidal glycoprotein
Indications for vancomycin
DOC for MRSA
First line: infection by penicillin-resistant Strep pneumoniae
Use restricted to tx of severe infection by beta-lactam-resistant GP organisms (Strep and Staph)
Primary indication of parentral vancomyicn is endocarditis or sepsis due to MRSA
First line agent for tetanus due to clostridium tetani
Also indicated for treatment of GP infection in patient allergic to beta-lactam
How is vancomycin administered
Commonly in combination with an aminoglycoside (gentamicin) for treatment of enterococcal infection (Synergistic bactericidal effect) in beta-lactam allergic patient
Employed orally for antibiotic-associated colitis due to staph or C. defficile overgrowth
Resistance to vancomycin
Plasmid-mediated reduction in drug permeability or altered target site
Administration of vancomycin
Not absorbed orally
Treatment of systemic infection by slow I.V. infusion
Inflammation allows it to penetrate meninges
Only orally for treatment of antibiotic-induced enterocolitis
Metabolism and excretion of vancomycin
Metabolism is insignificant
Excreted by glomerular filtration, so dosage must be altered in renal insufficiency
Adverse effects of vancomycin
Fever, chills, and/or phlebitis at site of infection
Flushing and shock due to histamine released following rapid infusion
How does daptomycin work?
Bactericidal (concentration dependent killing) through depolarization of membrane potential; leads to cell death through inhibition of proteins, DNA, and RNA synthesis
Antibacterial spectrum of Daptomycin
Active against GP bacteria
Similar spectrum to vancomycin; also synergistic with aminoglycosides
Indications for daptomycin
Complicated skin and soft tissue infections, bacteremia, endocarditis
Very active against S. aureus, MRSA, VRSA
Strep pyogenes, Strep agalactiae, Enterococcus faecalis (VRE), Enterococcus faecium (VRE)
Administration, metabolism and excretion of daptomycin
Must be given by I.v.; metabolism is unclear, but it is inactivated by pulmonary surfactant; 80% excreted by glomerular filtration, so dose must be modified in renal insufficiency
Adverse effects of daptomycin
GI distrubances: constipation, nausea, diarrhea, vomiting
Headache, insomnia, dizziness
Injection site reactions and skin rashes
Abnormal liver function tests, jaundice, renal failure
Fosfomycin (monurol) mechanism
Inhibits bacterial cell walls; resistance by decreased permeability; synergistic with aminoglycosides, beta lactams, or fluroquinolones
Use of fosfomycin
GP and GN organisms; Only orally; uncomplicated UTI (acute cystitis) and is safer during pregnancy; major indication is single dose treatment of UTI in female due to E. coli or Enterococcus faecalis
Second-line tuberculostatic agent, since it is not more active than first-line but hase more adverse effects;
Active against many GP and GN organisms, although it isn't really used for this
Pharmacokinetics of cycloserine
Widely distributed in body fluids, including CSF; metabolized to an extent; both cycloserine and metabolite eliminated by kidneys; accumulation occurs in those with renal failure
Adverse effects of cycloserine
CNS toxicity including headaches, tremors, psychosis, convulsion; peripheral neuropathy
Polymixin B mechanism
Behave like cationic detergents; bind to and disrupt bacterial cell membranes; tey are bactericidal for several GN rods
Polymixin B spectrum
Effective against GN rods, including Pseudomonas
Spectrum also includes E. coli, Enterobacter aerogenes, H. influenzae, Klebsiella pneumoniae, Shigella; GPs, as well as Preteus, Serratia, Nisseria are resistant to polymixins
Pharmacokinetics of polymixin B
Sulfate salt of polymixin B is water soluble and very stable in solution; however poorly distributed to tissues
Thus, mostly limited to topical applications in ointments with neomycin or bacitracin for superficial skin lacerations
Systemic use rare due to potential for nephrotoxicity and neurotoxicity; available for parentral use in UTI and bacteremia due to susceptible GN organisms when other antibiotics are contraindicated or ineffective
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